Opioids treat chronic pain by dulling its sensation in the brain and hijacking the brain’s reward system, which triggers the release of dopamine and feelings of pleasure. This is what makes the drugs so effective — and so addictive.

An estimated 2.7 million people in the U.S. are hooked on opioids despite widespread public health warnings and media attention focused on the dangers of opioid addiction. In 2022, roughly 82,000 deaths in the U.S. were linked to opioids.

This epidemic of opioid addiction is a big reason why investigators continue to search for alternative pain relievers. And they may have found one that doesn’t affect the brain —  despite its mind-altering source…

Cannabis-derived, sobriety ensured

Marijuana, also known as cannabis, has been used medicinally for thousands of years, including to treat pain. However, its status as an illegal drug and its effects on the mind have kept researchers from fully exploring its potential as a pain reliever.

Natural molecules found in the cannabis plant, referred to as cannabinoid molecules, are the source of the mind-altering properties of marijuana. They bind to the cannabinoid receptor one (CB1) on the surface of brain cells and pain-sensing nerve cells throughout the body.

Researchers at Washington University School of Medicine in St. Louis and Stanford University designed a cannabinoid molecule with a positive charge, preventing it from crossing the blood-brain barrier while allowing it to engage CB1 receptors elsewhere in the body. This compound, unlike cannabis, is modified to only bind to pain-sensing nerve cells outside the brain, thereby achieving pain relief without the usual mind-altering effects of cannabis.

The researchers tested the modified synthetic cannabinoid compound in mouse models of nerve-injury pain and migraine headaches, measuring the mice’s hypersensitivity to touch as a proxy for pain. They then applied an ordinarily non-painful stimulus to indirectly assess pain in mice.

The results were impressive — injections of the compound eliminated touch hypersensitivity in both mouse models. And since the compound doesn’t affect the brain, it avoids the mind-altering side effects and abuse potential of opioids.

“The custom-designed compound we created attaches to pain-reducing receptors in the body, but by design, it can’t reach the brain,” says the study’s senior author, Dr. Susruta Majumdar, a professor at WashU Medicine. “This means the compound avoids psychoactive side effects such as mood changes and isn’t addictive because it doesn’t act on the brain’s reward center.”

Using CBD for pain

Given its long-term effectiveness and its lack of tolerance, this cannabinoid compound holds great promise as a nonaddictive pain reliever. It could potentially provide relief to the estimated 50 million chronic pain sufferers in the U.S. This news may bring a sense of hope and optimism for those struggling with chronic pain. Moving forward, the researchers plan to develop the compound into an oral drug and evaluate it in clinical trials.

Until then, what can chronic pain sufferers do to manage their pain without resorting to dangerous opioids?

Well, there’s always cannabis itself. There’s a lot of evidence that the two primary compounds in cannabis — tetrahydrocannabinol (THC) and cannabidiol (CBD) — provide pain relief. One study even found that cannabis reduced pain in 95.9 percent of cancer sufferers who tried it.

Now that cannabis is legal in many states, it’s easier to acquire and use to treat pain. Just make sure you get Cannabis indica, which is the strain shown to be more effective for pain relief.

If you’re leery of the cannabis “high,” give CBD a try. CBD has many of the same anti-inflammatory and pain-relieving properties as cannabis, but you don’t get high from using it. Just make sure you get a high-quality CBD supplement that’s guaranteed to contain the amount of CBD it says it does.

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Sources:

Compound harnesses cannabis’ pain-relieving properties without side effects — EurekAlert!

A cryptic pocket in CB1 drives peripheral and functional selectivity — Nature

Medications to Treat Opioid Use Disorder Research Report — National Institute on Drug Abuse

Can cannabis help relieve pain? — Harvard Health Publishing